This project is concerned with a group of tetrahydroisoquinoline (TIQ) alkaloids that are formed spontaneously in a condensation reaction between catecholamines (such as dopamine, norepinephrine, epinephrine, L-dopa) and acetaldehyde. The acetaldehyde arises naturally as an intermediate in the metabolism of ethanol. We are investigating the possibility that the pharmacologic properties of TIQ alkaloids are responsible for alterations in neuronal function (catecholamine neurons) and, thereby, alterations in behavior after the ingestion of alcoholic beverages. It has already been shown that TIQs interact in meaningful ways with catecholamine neurons and their receptors. TIQs are taken up and stored by nerve terminals, they are released by electrical or chemical stimulation, and they interact with catecholamine receptors. Both agonist and antagonist actions have been observed. TIQs also compete with catecholamines for certain enzymatic processes relevant to neuronal function (e.g., transport mechanisms, binding in vesicles, metabolic enzymes). The current research proposal utilizes animal models and is directed towards the following main points: 1. measurement of TIQs at adrenergic loci in brain; 2. evaluation of certain behavioral and pharmacologic properties of the TIQs; and 3. evaluation of the properties and relevance of O-methylated "metabolites" of the TIQs. The long range goal is to answer the following questions: Are TIQ alkaloids responsible for behavioral changes after ingestion of alcoholic beverages? Can an understanding of the properties of TIQs lead to better approaches to the prevention and/or treatment of alcoholism?